Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.
Six times between 1816 and 1926 pandemics of cholera (Vibrio cholerae) decimated the world’s populations. An abbreviated rap sheet looks like this:
1816: The first pandemic of modern times struck India. By 1824, it had spread west to China and the Philippines and east to Japan, sowing death along its path.
1829-1852: The second pandemic raged through North Africa and jumped into Europe. It killed 7,000 Londoners in 1832. That year saw cholera leap the Atlantic to North America, and on in 1834 from New York to the Pacific Ocean, then south into Mexico and South America. From Cuba it cut north to Canada in 1849. In 1849, cholera killed over 50,000 people in the British Isles. Then, on Sept. 7, 1854, a prominent anesthetist, John Snow, convinced the British Board of Guardians to remove the water-pump handle serving London’s Broad Street. Cholera infection and death quickly dropped, proving that the disease was caused by fecally contaminated water from the city’s faulty sewers.
1847-1861: The third pandemic took 5,000 lives in New York City, and 1 million in Russia, of 2,589,843 infected.
1863-1875: The fourth pandemic was spread by returning Islamic pilgrims from Arabia to Egypt, then crossed the Mediterranean into Italy, France and onward.
1892: A fifth, more limited, epidemic struck Hamburg, Germany.
1899-1926: The sixth onslaught, skirting Europe except for the Balkans, ravaged Russia anew.
1961-1993: Following the sixth pandemic, cholera flared for the seventh outbreak in 1961. This time it started in Indonesia’s island of Sulawesi, then rampaged through Asia and Africa to infect 29 countries in two years. By 1991, the lengthiest cholera pandemic yet struck Peru, causing 150,000 cases in three months. By early 1992, the infection struck 400,000 men, women and children throughout Latin America, killing 4,000.
In 1993, a new strain of the pathogen, 0139, erupted in India and Bangladesh, where 5,000 succumbed. Strain 0139 now is being looked at apprehensively by some scientists as perhaps portending pandemic number eight.
2000: Vibrio cholera’s 4,033,460 base pairs were sequenced by TIGR The Institute for Genomic Research in Rockville, Md. Nature announced that feat in an article titled: “DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.” Its three co-senior authors are TIGR’s J. Craig Venter and Claire Fraser, plus John Mekalanos, a leading cholera vaccine developer at Harvard Medical School. (See BioWorld Today, Aug. 3, 2000, p. 1.)
Mekalanos is senior author this month of a paper in the Proceedings of the National Academy of Sciences (PNAS) dated Feb. 5, 2002. Its title: “Comparative genomic analysis of Vibrio cholerae: Genes that correlate with cholera epidemic and pandemic disease.”
“The completed genome sequence of 7th pandemic El Tor 01 N16961 strain,” the article observed,” has provided an important tool to begin addressing questions about the evolution of V. cholerae as a human pathogen and environmental organism.” Whereupon, Mekalanos and his co-authors constructed a V. cholerae genomic microarray that displayed more than 93 percent of the predicted genes in that strain. They went on to identify genes unique to all pandemic strains, as well as those specific to 7th pandemic’s El Tor. “These later genes,” the co-authors pointed out, “may encode gain-of-function traits specifically associated with displacement of the pre-existing classical strains in South Asia.” They added grimly that these “may also promote the establishment of endemic disease in previously cholera-free locations.”
Pre-implant Diagnosis Lets Woman Foredoomed To Early Onset Alzheimer’s Birth A Healthy Girl
A 30-year-old woman diagnosed with a gene mutation that will cause her to contract early onset Alzheimer’s disease has given birth to a daughter certified free of an inherited predisposition to the disease. Today’s Journal of the American Medical Association (JAMA), dated Feb. 27, 2002, reports the unusual story under the title: “Preimplantation diagnosis for early onset Alzheimer’s disease caused by V717L mutation.”
Its principal author is geneticist Yuri Verlinsky, director and president of the private Chicago-based Reproductive Genetics Institute. An accompanying commentary is headed: “Ethics of preimplantation diagnosis for woman destined to develop early onset Alzheimer’s disease.”
“This V717L specific familial genetic mutation was discovered in three of the woman’s five family members,” Verlinsky told BioWorld Today. He then described the procedure,which combines elements of in vitro fertilization and DNA testing of embryos. “We took cells from the developing egg’s polar body,” he recounted, “put them in special buffer and then to PCR. We designed special primers upstream and downstream to amplify this side of the gene so we could determine if it was going to be normal or abnormal.
“The clinical side was to stimulate the woman with gonadotropins to produce a lot of oocytes. In this case it was the gene. Then we did a biopsy by micromanipulation, sectioned the zona pellucida and on to buffer. In the second part of the process,” Verlinsky continued, “the embryo went to fertilization, and the next day we examined it to make sure of the diagnosis. From the 13 embryos in vitro, we selected six normal; seven were abnormal. Four were developing to the stage we like to transfer. So one embryo was implanted in a single pregnancy. The baby girl was born about 15 months ago.”